Preterm
progress
DR ANNE GALLAGHER
Dr Anne Gallagher provides an insight
into the novel neuroimaging techniques
that her research programme is
developing to better serve the needs
of babies born prematurely
Could you outline your overarching
research interests?
I currently direct the Laboratory of Optical
Imaging in Neurodevelopment (Laboratoire
d’Imagerie Optique en Neurodevelopement –
LION’s Lab) within the University of Montreal’s
Psychology Department and the Sainte-Justine
University Hospital Research Center. Imaging
the brains of healthy and epileptic infants and
children constitutes a significant part of my
research programme.
Additionally, a few years ago I began investigating
the cerebral development of premature babies.
Our research programme on preterm birth
aims to identify cerebral markers predictive of
neurodevelopmental outcomes. Identification of
such predictive markers is crucial in premature
children since cognitive and behavioural sequelae
are often highlighted when the child starts
school, when greater demands are placed on
cognitive and psychosocial skills. Late diagnosis
and interventions can lead to repeated setbacks
in their education, which can have a dramatic
impact on psychosocial development. We
believe that identification of predictive markers
during the pre-school period would enable the
provision of earlier interventions, improving
neurodevelopmental outcomes.
How have you seen perinatal care develop
over recent years, and to what extent has this
shaped your work?
For the past several years, tremendous medical
progress has been made in the perinatal care
of preterm infants. This has significantly raised
the survival rate. However, probably due to the
paramount importance of the final gestational
weeks on brain development, the incidence of
sensory deficits (eg. visual impairments) and
neurodevelopmental disorders (eg. attention
deficits with/without hyperactivity disorder
(ADHD), learning disabilities, communication
deficits) remains unchanged. This growing
population of children with special needs
drove us to study the sensory and cognitive
development of children born prematurely in
order to identify early markers of behavioural
and cognitive impairments. We hope this will
lead to the creation of adapted intervention
strategies to improve neurodevelopmental and
schooling outcomes.
What is the relationship between
visual processing and cognitive
development deficits?
We believe that impairments in visual processing
may lead to cognitive deficits and learning
disabilities such as dyslexia at school age. Our
results so far have confirmed that preterm
infants show developmental delays in visual
processing as early as three months of age,
which then persist throughout childhood. In
a first set of electroencephalography (EEG)
studies, we aimed to characterise early visual
processing development in preterm children.
Now, we have to better study the relationship
between early visual impairments and
neuropsychological outcomes.
Could you describe your work on the
development of predictive markers for
neurodevelopmental deficits?
In addition to early visual processing, we are
investigating other predictive markers of
neurodevelopmental outcome. One of my
PhD students, Natacha Paquette, recently
obtained some very interesting results in this
area, using electroencephalography (EEG)
to identify abnormal auditory and attention
processing of verbal stimulation in three-,
12- and 36-month-old preterm infants. She
demonstrated that altered neuronal responses
in three-month-olds are associated with lower
cognitive and language functioning at 36
months, and so might be used as predictive
markers for neurodevelopmental impairments.
Her EEG paradigm could thus be employed to
early identify children at high risk of presenting
neuropsychological impairments, such as
expressive language problems or attention
deficit disorder. We continue following these
children who are now almost 10 years old.
We are interested in their neuropsychological
profile, social abilities and school functioning,
and we keep studying their brain development.
In what way do you envision your work
will contribute to the care of children
born prematurely throughout the rest of
their lives?
In the near future, we hope that identification of
early predictive markers will have direct impacts
on the clinical management of children born
prematurely. Specific and early interventions
should be developed and eventually offered
to those who will be identified at high risk
for cognitive and language delay as well as
learning disabilities. Indeed, a long-term goal
of our research programme is to develop earlier
specialised interventions for these children.
In collaboration with a multidisciplinary
team, we plan to launch a research project
to assess the impact on cognition and brain
development of an early intervention programme
in pre-school children born prematurely
who have been identified to be at high-risk
of developing cognitive and language delay.
Based on my clinical experience as a paediatric
neuropsychologist, I believe that implementation
of such early strategies can have a major impact
on the neurodevelopmental outcome. Later, it
should benefit these kids for school functioning,
socialisation and quality of life during childhood,
adolescence and even adulthood.
Natacha Paquette
in the lab
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DR ANNE GALLAGHER
Insightful imaging
In the Sainte-Justine University Hospital Research Center, Canada, a dynamic
team of scientists are using their imaging expertise to devise ways to identify
indicators of future difficulties in preterm children at the earliest opportunity
PRETERM BIRTHS – those that occur before 37
weeks of gestation – are a common occurrence;
in fact, the Centers for Disease Control and
Prevention (CDC) calculate that one in every
eight infants in the US is born prematurely. At
present, due to the tremendous progress that
has been made in recent years in the field of
perinatal medicine, infants born prematurely
are more likely to survive than ever before.
However, preterm survival does not necessarily
equate to preterm health and, despite medical
advances, preterm birth remains a leading cause
of long-term morbidity worldwide. Studies have
consistently shown that infants born prematurely
are more likely to be affected by a host of
sensory, cognitive and behavioural impairments.
Although some difficulties can be diagnosed
early in infancy, many cognitive and behavioural
deficits are not recognised until several years
later, often when the child is beginning school
and when the opportunity for effective early
interventions has already passed. It is for this
reason that researchers are now searching for
early markers predictive of these disabilities, as
a means to better screen and help this growing
population of prematurely born children. One
such scientist is Dr Anne Gallagher.
THE LION’S LAB
Gallagher is the Director of the Laboratory
of Optical Imaging in Neurodevelopment
(Laboratoire
d’Imagerie
Optique
en
Neurodevelopement) – better known as
the ‘LION’s lab’ – within the Sainte-Justine
University Hospital Research Center in Canada.
She is also Assistant Research Professor of
Psychology at the University of Montreal. “I
have been fascinated by brain research and
paediatric neuropsychology ever since my first
year as an undergraduate student, when I was
introduced to the topic of brain development
during a neuroscience class,” Gallagher recalls.
She pursued this interest throughout her PhD
and postdoctoral training at the University of
Montreal and Harvard Medical School, studying
healthy brain maturation and paediatric epilepsy
before extending her research interests to
include neurological development in preterm
infants and children.
During her career, Gallagher has used an evergrowing array of child-friendly neuroimaging
techniques to assist her investigations,
including
near-infrared
spectroscopy
(NIRS),
electroencephalography
(EEG),
magnetoencephalography (MEG) and magnetic
resonance imaging (MRI). Along with coworkers, Gallagher hopes to utilise the team’s
wealth of experience in paediatric neuroimaging
50
to identify predictive markers for a variety of
cognitive and behavioural disorders commonly
diagnosed in preterm children once they reach
school-age.
To date, the team has made considerable use
of evoked potentials – electrical potential
records of the nervous system’s response to
specific stimuli, which can be obtained using
EEG. “Compared to the 19 electrodes typically
used for clinical EEG recording, we use at least
128 electrodes. This allows us to perform
sophisticated analyses on electrical brain
signals,” Gallagher enthuses. “By comparing
evoked potentials in preterm and healthy
infants and children, we can look for abnormal
or delayed brain development associated with
prematurity.” There is therefore the possibility
that evoked potentials could be used for the
identification of early biomarkers of learning
disabilities or neurodevelopmental disorders.
The researchers do not rely on evoked potentials
alone, however, as Gallagher explains: “Evoked
potentials are very good at giving specific
information on the timing of the brain response,
but they are not very accurate at localising it”.
For this reason, Gallagher and her collaborators
employ cutting-edge multimodal neuroimaging
– the simultaneous utilisation of evoked
potentials and near-infrared spectroscopy
(NIRS) – in order to obtain both temporal and
spatial data.
THE FUTURE IN THEIR EYES
As visual impairments in infancy constitute
the major sensory sequelae of prematurity, the
group has invested considerable time looking
at the usefulness of early visual impairments
as predictive markers for later cognitive
or behavioural disorders or difficulties. The
investigators found that developmental delays
in visual cerebral pathways in premature
infants – that can be identified as early as
three-months-old persist and can still be
detected as late as seven- or eight-years-old.
At school-age, these children also show higher
prevalence of attention deficits with/without
hyperactivity disorder (ADHD) and learning
disabilities than fullterms. These findings add to
the body of evidence suggesting that abnormal
visual system development in preterm children
may be associated with cognitive and learning
disabilities later on. Additional research is now
required, however, to further delineate the exact
neurological relationship between visual brain
system development and cognitive deficits and/
or learning disabilities.
PAYING ATTENTION TO ATTENTION
More recently, the team has turned its attention
to establishing how early deficits in attention
and language development could be used as
predictive markers for later problems, such as
language disorders or ADHD. Using EEG, the
group has identified abnormal auditory and
attention processing development by measuring
neurological responses to verbal stimulation in
both preterm and fullterm children at the ages of
3-, 12- and 36-months of age. The scientists also
confirmed that infants with lower birth weight
and younger gestational age are associated with
greater visual and cognitive delays.
A number of significant discoveries have been
made as a result of this research programme,
Figure 1. The left-panel picture shows a three-month old baby wearing a 128-electrode EEG cap. On the right
panel, EPs result from visual cortical areas during a visual stimulation comparing fullterm (blue) and preterm
(red). Significant differences between both groups (shown by *) reveal brain developmental alterations in the
premature brain. Although pretem infants overcome the visual developmental delay over the first year after birth,
source analyses (bottom) performed at 12 months of age show different brain activations between the groups,
suggesting brain reorganisation in babies born prematurely.
INTERNATIONAL INNOVATION
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for instance, novel neuroimaging techniques
have revealed developmental delays for verbal
attention processing, but not non-verbal
attention processing, at three-months-old. This
suggests that babies born prematurely are more
likely to be affected by language processing
alterations than their fullterm counterparts.
This suggests that evoked potentials could be
utilised as early markers for later cognitive and
behavioural deficits, and that preterm patients
may benefit from the implementation of evoked
potential measurements during their infancy
from as early as three months. So far, the group
has successfully identified 3-month evoked
potential markers predictive of global cognitive
functioning and language development at 36
months of age.
MAKING CHANGES
Now that the scientists have a clearer picture
of potential early cerebral markers for cognitive
and behavioural disabilities, the link between
the two need characterising; at present, the
exact nature of the relationship between
these predictive markers and the subsequent
disorders are unknown. “We aim to identify
more early predictive cerebral markers of
neurodevelopmental disabilities and to
better understand the neuropsychological
manifestations of preterm children and
their cerebral correlates using a multimodal
INTELLIGENCE
SENSORY AND COGNITIVE DEVELOPMENT
IN CHILDREN BORN PREMATURELY
OBJECTIVES
• To identify cerebral markers predictive of
specific neurodevelopmental impairments
Anne Gallagher with lab coordinator
and senior electrophysiology technician,
Phetsamone Vannasing.
neuroimaging approach,” outlines Gallagher.
To achieve the latter goal, the team will utilise
evoking potentials and NIRS to measure
haemodynamic neurological changes and
localise cerebral activity.
The main aim is to use the insights gained to
better predict a preterm child’s neurological
and cognitive future and, in so doing, enable the
implementation of well-timed, effective and
early intervention and rehabilitation strategies.
Gallagher is also hopeful that her team will
ultimately play an instrumental role in the
shaping of such strategies. “As a long-term goal,
we will work on the development of intervention
strategies for pre-school children in order to
prevent, or at least reduce, the incidence of
cognitive and behavioural disorders in these
children,” she states.
• To better understand the cerebral correlates of
neuropsychological manifestations
• To develop early specialised interventions for
infants who have been identified at high risk for
cognitive and language delay as well as learning
disabilities (long-term objective)
KEY COLLABORATORS
Dr Maryse Lassonde; Dr Franco Lepore; Dr
Michèle McKerral; Dr Francine Lefebvre,
Sainte-Justine University Hospital Center and
Université de Montréal
Dr Pedro Valdes-Sosa; Dr Maria Luisa Bringas,
Cuban Neuroscience Center, Havana, Cuba
Dr Fabrice Wallois, University of Picardie Jules
Verne, Amiens, France
KEY LAB MEMBERS
Phetsamone Vannasing; Julie Tremblay,
Eng., Laboratory of Optical Imaging in
Neurodevelopment, University of Montreal’s
Psychology Department and the Sainte-Justine
University Hospital Research Center
FUNDING
Canadian Institutes of Health Research (CIHR
• Fonds de la Recherche du Québec – Santé
(FRQS)
CONTACT
Dr Anne Gallagher
Assistant Research Professor
Psychology Department
University of Montreal
CHU Sainte-Justine Research Center
3175 Chemin de la Côte Sainte-Catherine
Montreal, Quebec H3T 1C5, Canada
T +1 514 345 4931 x 6409
E [email protected]
DR ANNE GALLAGHER completed her
postdoctoral training at the Harvard Medical
School, Massachussetts General Hospital and
Athinoula A Martinos Center for Biomedical
Imaging, Boston, USA in 2011. She received
her PhD in Research and Intervention from
the Clinical Neuropsychology Option at the
University of Montreal in 2008. She is the
recipient of two major Salary Awards from the
CIHR and FRQS.
There is the possibility
that evoked potentials could
be used for the identification of early
biomarkers of learning disabilities
or neurodevelopmental disorders
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